In search of cure for neurological disorders a previously abandoned class of medications called Psychedelic and their active derivatives particularly Psilocybin, a tryptamine like compound has regained the research interest. Emerging scientific evidence support the psychedelic therapeutic benefits beyond Major depressive disorder (MDD) and substance use disorder (SUD). Recently collected encouraging results have already led to bestow these agents with a "Breakthrough Therapy" status by FDA for long term treatment of major psychiatric illness particularly MDD. Additionally, in vivo and in vitro research findings points towards psychedelic therapeutic potential for treatment and prevention of close brain injury and neurodegenerative disorders such as Alzheimer disease. Although psychedelic's complete molecular mechanism imparting there therapeutic effect is yet to be determined but preclinical work has uncovered the psychedelic ability to induce neural progenitor cell proliferation, spinogenesis, synaptic rebirth and increase in neuroplasticity via various complex biochemical mechanisms. These agents have also demonstrated significant immunomodulator potential by reducing pro inflammatory agents such as tumor necrosis factor alpha (TNF-α), Interleukin1-Beta (IL-β) and Interlukin-6 (IL-6) contributing to their healing power. Although the definite role of psychedelic benefits beyond MDD and SUD yet to be determine, but if scientific data is successfully replicated in clinical trials psychedelics can develop into revolutionary treatment modality for multiple neuropsychiatric conditions along with previously approved treatment of psychiatric disorder. In this review author discuss recent scientific research and study results pertaining to psychedelics therapeutic effects at cellular level in central nervous system with emphasis on neurodegeneration. Abbreviations/ Keywords: BDNF; Brain-derived neurotrophic factor, BBB; Blood-brain barrier, CNS; Central nervous system, DMT; N,N dimethyl tryptamine, ERS; Endoplasmic reticulum stress, FDA; food and drugs administration, fMRI; Functional magnetic resonance imaging, IL; interleukin, LSD; Lysergic acid diethyl amide, MMD; Major depressive disorder, Nrf2; Nuclear factor erythroid2-related factor 2, Rac 1; Rat-related C3 botulinum toxin substrate 1, RhoA; Ras homolog family member A, TAAR; Trace amine-associated receptor, Tj; Tight junction, Tumor necrosis factor alpha (TNF-α), Tropomyosin receptor kinase B; (TrkB). SUD; Substance use disorder. Method: To investigate the role of Psychedelic in neurodegeneration the PubMed and Google scholar databases were searched for terms like psychedelic, 5-HT receptor serotonin, neuropsychiatric role of psychedelics, recent clinical trial and psychedelic, neuroprotection, immunomodulation, neurodegenerative mechanisms , psychedelic and recent break through studies and treatments. Additional search of reference articles was carried out and related articles were chosen for review Pertinent articles describing the historical preview, biochemical properties, mechanism of action of Psychedelic in neuro psychiatric conditions and their effect on related symptoms in different settings, both in vivo and in vitro models were selected. Only reviews, analyses, meta-analyses, and randomized control-based studies were included in the search criteria. The focus of the search was on adults, regardless of specific age, race, or gender. Only articles written in English, published within last ten years and with free access were included.